Clinical Trials Phase 0

Traditionally, all clinical trials for new drugs started with phase 1, which aims to test a drug’s safety and effectiveness. Today, however, some clinical trials begin with phase 0. This type of trial is used to verify a new drug’s mode of action before addressing its efficacy and safety.

Primary Purposes of a Phase 0 Trial

Phase 0 clinical trials were introduced in 2007, in response to concerns from the U.S. Food and Drug Administration (FDA). The FDA had observed that while research on new drugs was increasing, fewer drugs were actually making it to market. FDA officials thought that the time and expense of all these failed clinical trials might have been hindering the discovery of beneficial new drugs.

A phase 0 trial aims to determine if a drug has enough potential to advance to a phase 1 trial and beyond. Phase 0 trials require a small number of volunteers (often 12 or less) and use doses of the drug that are too low to be considered therapeutic.

In determining if a drug has such potential, researchers examine the drug’s activity in the body, specifically its pharmacodynamics and pharmacokinetics:

Pharmacodynamics refers to a drug’s effects on the body at the cellular and molecular levels, such as how and where the drug is absorbed and with which proteins the drug interacts.

Pharmacokinetics refers to a drug’s long-term activity in the body, including how and when it is excreted.

If the pharmacodynamic and pharmacokinetic data indicate that a drug’s activity isn’t as researchers had hoped, the clinical trial doesn’t advance to phase 1. Researchers are then free to pursue more promising drug candidates.

When Is a Phase 0 Trial Used?

A phase 0 trial may be included in clinical trials for novel drugs—also known as investigative new drugs. These drugs are newly developed chemical agents that have never been on the market before and haven’t been tested in humans.

Novel chemotherapy drugs, in particular, may benefit from a phase 0 clinical trial. Chemotherapy drugs are designed to specifically target cancer cells, but can have toxic effects on other tissues, as well. Phase 0 trials can determine the specificity of a drug’s activity, which is an especially important consideration for new chemotherapy drugs.